The principal objective of this study is to increase our understanding of the primary causes of cataract formation in the human. Animal lenses will be used initially; when and where appropriate, clear and cataractous human lenses removed at the time of cataract extraction, enucleation, or autopsy, will be used. Attention will be focused on the factors regulating anaerobic glycolysis, the principal source of biological energy in the lens. Hexokinase, the pacemaker of this metabolic pathway and phosphofructokinase, an equally important point of metabolic control, will be studied in detail. Isolation and characterization of these enzymes will be attempted. Changes in overall glycolytic activity will be correlated with changes in hexokinase and phosphofructokinase activity. A well developed lens-culture system will be used to study an experimental analogue of the "hypoglycemic" cataract; it is in this type of cataract that a link between decreased hexokinase activity, disordered glycolysis and cataract formation may be substantiated. Well established biochemical and physiological techniques will be employed in all these studies. A continuing effort will be made to extend and compare results with the animal lens to the human lens. BIBLIOGRAPHIC REFERENCES: Chylack, L.T., Jr., Bienfang, D.C., Bellows, A.R. and Stillman, J.S.: Ocular manifestations of juvenile rheumatoid arthritis. Amer. J. Ophthalmol. 79:1026, 1975. Chylack, L.T., Jr., Mechanism of "hypoglycemic" cataract formation in the rat lens. I. Role of hexokinase instability. Invest. Ophthalmol. 14:746, 1975.